When the normal blood supply a person's heart muscle is disrupted, the person may suffer what is commonly termed a heart attack. Heart attacks are one of the major health problems in the world. In the United States alone there are over 1.1 million heart attacks a year. Of those 1.1 million victims, about 250,000 die within 1 hour. However, those that survive the initial heart attack generally subsequently receive treatment. In fact, about 375,000 of those heart attack victims will make it to a hospital for treatment within 1 hour; about 637,000 will make it to a hospital for treatment within 4 hours. Unfortunately, when treated using current methods, heart attacks often result in serious and permanent damage to the heart muscle. In fact, it is estimated that about 66% of the MI patients do not make a complete recovery, but rather suffer permanent injury to cardiac muscle cells. An effective treatment that minimizes permanent damage to the heart as a result of the heart attack would be of great value to these patents.
In a typical heart attack, there is a blockage in an artery that provide blood to some of the cardiac muscle cells, so the cells in the affected portion of the heart (termed the area at risk) experience ischemia, or a lack of adequate blood flow. This ischemia results in an inadequate supply of oxygen for the muscles and inadequate removal of waste product of muscle activity such as CO2, lactic acid or other by-products of metabolism. These substances may therefore reach toxic concentrations and thus, in turn, cause serious long-term consequences such as the breakdown of the cell walls, release of toxic enzymes or the like, and ultimately result in the death of many or all of the cardiac muscle cells in the area at risk.
The ischemia, however, is not always permanent. In fact, if the heart attack does not result in the immediate death of the individual, the ischemia is generally reversed either spontaneously or with medical intervention. If the ischemia is a result of blockage of an artery by a blood clot, the clot may spontaneously dissolve in the ordinary course of time due to the body's own natural thrombolytics, and blood may again flow to the affected area. Alternatively, medical treatment may restore blood flow. Such medical treatments include administration of thrombolytic drugs, such as tPA, to dissolve blood clots in the vessels of the heart to restore blood flow, balloon angioplasty, where an interventional cardiologist steers a catheter with a balloon on the end into the clogged artery and inflates the balloon to open the artery, coronary stenting, where an interventional cardiologist steers a catheter with a stent on it into the clogged vessel and expands the stent to place what amounts to a scaffold into the vessel with the blockage to hold the vessel open, or coronary by-pass surgery where a blood vessel is harvested from elsewhere in the patient's body and is attached around a blocked coronary artery to restore blood to the ischemic tissue distal of the blockage. These treatments may be applied individually or in concert with one or more of the other treatments.
Generally if the ischemic event is for a short period of time or oxygenated blood is available to the affected tissue from another blood supply, for example from collateral arteries or even from blood within the heart cavity, some or all of the muscle cells in the area at risk may survive and ultimately recover much or all of their function. However, if the period of ischemia is long enough and severe enough, the cardiac muscle cells in the area at risk may in fact die as a result of the ischemic insult. The area of dead tissue resulting from this cell death is called an infarct and the area may be said to be infarcted.
Unlike many cells in the body, for example, skeletal muscle cells, cardiac muscle cells do not significantly regenerate. Thus an infarcted region of cardiac muscle cells will generally be a permanently non-functioning portion of the patient's heart. This will result in decreased overall heart function, which may lead to systemic vascular insufficiency, congestive heart failure, and even death. It is thus of great importance to minimize the amount of infarct that results from cardiac ischemic events.
Infarct may result from heart attacks as described above, and may also result from myocardial ischemic events as the result of other causes and may even be predicable. For example, in so-called beating heart by-pass surgery, the surgeon stops the heart for short periods of time to sew grafts onto the surface of the heart. In such a procedure, the heart is deprived of blood during the time that circulation is stopped, and unless protected, infarct can result from this ischemic event.
Another common interventional procedure, cardiac balloon angioplasty, also disrupts the blood supply to part of the heart and results in predictable ischemia. In balloon angioplasty of the heart, an interventional cardiologist inserts a balloon catheter into the vasculature of the heart with the balloon deflated. The balloon is placed at a location where the interventionalist wants to dilate the vessel, and then inflates the balloon against the walls of the vessel. When the balloon is inflated, it fills the vessel in question and blocks most if not all blood from flowing through that vessel. In this way, it creates an area of ischemia downstream from the balloon, which ischemia persists for as long as the balloon is inflated. Although attempts have been made to relieve this ischemia by means of catheters that allow perfusion from one side of the balloon to the other during inflation (so called auto-perfusion balloons), these have generally proven to be inadequate.
It is also sometimes the case that during or after angioplasty the dilated vessel is either dissected or goes into spasm. If the vessel spasms shut or is dissected, the blood supply to all the tissue vascularized by the artery in question suffers severe ischemia and potential infarct. In such cases the patient is generally taken to a surgical suite and open chest by-pass is performed. Until the by-pass is successfully completed, the area at risk remains starved of blood.
Medical practitioners have attempted to reduce the infarct resulting from the ischemic events suffered during beating heart surgery and angioplasty with drugs and through a technique known as preconditioning. Drugs, for example adenosine and RheothRx, have been tried, and although under some circumstances they may have some effect, they have ultimately proven generally inadequate for one reason or another.
In preconditioning, the cardiac muscle is subjected to short periods of ischemia, for example two or three episodes of 5 minutes of ischemia followed by reperfusion, prior to the angioplasty or other anticipated procedure that will expose the heart to a more prolonged ischemic event. This has been found to reduce the infarct size resulting from the prolonged subsequent ischemia somewhat, but is difficult to perform safely, requires a complex set-up and is an invasive procedure. Importantly, precondition must occur well in advance of the ischemic event. For all these reasons it is generally not a useful procedure, and because it necessarily must occur in advance of the anticipated ischemic event, it is unsuitable for treating ischemia due to heart attacks that have already occurred or are in process.
Under ordinary circumstances, the temperature of the body and particularly that of the blood is maintained by the body's thermoregulatory system at a very constant temperature of about 37° C. (98.6° F.) sometimes referred to as normothermia. The amount of heat generated by the body's metabolism is very precisely balanced by the amount of heat lost to the environment. The circulating blood serves to keep the entire body and particularly the heart, at normothermia. Deep hypothermia (30° C. or lower) has long been known to be neuroprotective, and believed to be cardioprotective as well. More recently, the advantage of mild hypothermia (only as low as 32° C. or even as warm as between 35° C. and normothermia) to ischemic cardiac tissue has been recognized, either before and/or during an anticipated ischemic event such as may occur in beating heart surgery or coronary angioplasty, during an ischemic event such as a heart attack in progress, or soon after an ischemic event such as a heart attack that has already occurred. No satisfactory method of achieving this mild cardiac hypothermia in the human clinical setting, however, has been available before this invention. In rabbits, ice bags or ice-filled surgical gloves have been applied directly to the heart in an open-chest procedure. This method is clearly very invasive, clumsy and lacks control over the level of hypothermia applied. Other attempts have been made using cooling blankets or externally applied ice bags or iced blankets. These methods are slow, lack adequate control over the patient temperature, are not directed to the heart muscle and therefore are not effective in the human clinical setting to adequately reduce cardiac temperature, especially in obese patients.
Another method of achieving cardiac hypothermia has been proposed, that of pericardial lavage using a two-lumen catheter, with the distal ends of both lumens (one input and one outflow) sealed inside the pericardial sack. A cold solution such as cold saline is circulated within the pericardial sack to cool the heart muscle. While this method is rapid and directed to the cardiac muscle, it is highly invasive, requires surgical access to the pericardial sack which generally requires either an open chest procedure or a thoracotomy, involves piercing the pericardial sack, and introducing superfluous fluid into the pericardial sack of a beating heart, all with the attendant risks. If used, it requires the full surgical suite and delicate and highly skilled surgical technique. The surgical invasion of the pericardial sack is generally not acceptable to practitioners.
Thus, although mild cardiac hypothermia provides protection against infarct resulting from a cardiac ischemic event, the existing methods of achieving cardiac hypothermia are inadequate and unacceptable; a better method of achieving mild hypothermia of the heart that is fast, controlled and less invasive is needed.